期刊
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
卷 27, 期 5, 页码 329-335出版社
MARY ANN LIEBERT INC
DOI: 10.1089/cbr.2012.1199
关键词
breast cancer; biotherapy; cancer; gene therapy; irradiation
类别
资金
- PCSIRT [IRT0849]
- NNSFC [81071906, 81172127]
- Ministry of Education of China [20103201120016]
- PAPD
- Major Program for the Natural Science Fundamental Research of the Higher Education Institutions of Jiangsu Province [SZ16933]
- U.S. NIH-NIGMS [R01GM063075]
- NCCAM [R01AT05076]
Our previous studies have shown that high-mobility group box 1 (HMGB1) could physically associate with the retinoblastoma (RB) protein via an LXCXE (leucine-X-cysteine-X-glutamic; X=any amino acid) motif. An identical LXCXE motif is present in the HMGB1-3 protein sequences, whereas a near-consensus LXCXD (leucine-X-cysteine-X-asparagine; X=any amino acid) motif is found in the HMGB4 protein. In this study, we have demonstrated that like HMGB1, HMGB2-3 also associated with the RB in vitro and in vivo, as evidenced by glutathione-s-transferase capture and immunoprecipitation-Western blot assays. A point mutation of the LXCXE or LXCXD motif led to disruption of RB: HMGB1-4 interactions. Enforced expression of HMGB1-3 or HMGB4 by adenoviral-vector-mediated gene transfer resulted in significant inhibition of breast cancer cell proliferation through an LXCXE- or LXCXD-dependent mechanism and an increased radiosensitivity through an LXCXE- or LXCXD-independent mechanism. These results suggest an important role of the LXCXE/D motif in RB: HMGB1-4 association and modulation of cancer cell growth, but not radiosensitivity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据